We describe a case of severe hypoglycemia in a 14-month-old child as a suspected adverse drug reaction (ADR) to nadolol, and we performed an analysis of the FDA Adverse Event Reporting System (FAERS) database. Although previous reports have identified the risk of severe hypoglycemia in children during treatment with β-blockers, little is known about hypoglycemia as an ADR in infants treated with nadolol. Moreover, the pharmacodynamic and pharmacokinetic profiles of nadolol in children aged less than 1 year old are still not fully known.
We extracted all ADR reports involving nadolol from the FAERS database; in order to reduce the risk of bias, we only considered cases that exclusively reported nadolol as the suspect drug. We then selected cases of hypoglycemia in the pediatric population and conducted a manual deduplication.
Upon FAERS database analysis, a total of 2,674 suspected ADR reports to nadolol were found. Of these, 1,950 (73%) were solely attributed to nadolol, and 63 of them were hypoglycemic events. A total of 47 reports included the relevant pediatric age (74.6%). After deduplication, we identified 25 cases (mean age 3.65 years old); all of these reports were categorized as serious, and hospitalization was required in 15 cases.
Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.
Hypoglycemia is a reported life-threatening ADR associated with nadolol, especially in infants, in whom this drug should be used with caution.Two marine bacterial strains, designated S2-4-21T and MT2-5-19, were isolated from two tidal flat sediments of cordgrass Spartina alterniflora and adjacent oyster culture field in Quanzhou bay, China, respectively. Both strains were Gram-staining-negative, rod-shaped, non-flagellated, non-motile, aerobic, had NaCl requirements, and contained carotenoid and flexirubin pigments. The 16S rRNA gene sequence similarity (99.8%), average nucleotide identity value (99.4%) and average amino acid identity (99.3%) between strain S2-4-21T and strain MT2-5-19 strongly supported that they belonged to a single species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S2-4-21T and strain MT2-5-19 formed a monophyletic branch affiliated to the family Flavobacteriaceae, sharing similarities of 94.6% with Euzebyella marina CY01T and E. saccharophila 7SM30T, and of 94.1 and 92.8% with E. algicola MEBiC 12267T and Pseudozobellia thermophile DSM 19858T, respectively. Phylogenomic analysis based on the whole genome sequences supported that the two strains formed a distinct monophyletic clade within Flavobacteriaceae members, which was phylogenetically different from the clades of Euzebyella and Pseudozobellia. The major respiratory quinone was menaquinone MK-6. The major fatty acids (&gt;10%) consisted of C15 0 iso, C16 0, summed feature 9 (C17 1 iso ω9c/C16 0 10-methyl) and C17 0 iso 3-OH. The polar lipid profiles of strain S2-4-21T and strain MT2-5-19 are identical, including phosphatidylethanolamine, four unidentified aminolipids, and four unidentified lipids. The genomic size was 4.9-5.0 Mb with genomic DNA G+C content of 41.5 mol%. Based on the above characteristics, strains S2-4-21T and MT2-5-19 represented a novel species of a novel genus in the family Flavobacteriaceae. Thus, Pareuzebyella sediminis gen. nov. sp. nov. is proposed with type strain S2-4-21T (=MCCC 1K03818T=KCTC 72152T), and another strain MT2-5-19 (=KCTC 72539=MCCC 1K03874).Introduction.Serratia marcescens is a bacterial pathogen that causes ventilator-associated pneumonia and ocular infections. The FlhD and FlhC proteins complex to form a heteromeric transcription factor whose regulon, in S. marcescens, regulates genes for the production of flagellum, phospholipase A and the cytolysin ShlA. The previously identified mutation, scrp-31, resulted in highly elevated expression of the flhDC operon. The scrp-31 mutant was observed to be more cytotoxic to human airway and ocular surface epithelial cells than the wild-type bacteria and the present study sought to identify the mechanism underlying the increased cytotoxicity phenotype.Hypothesis/Gap Statement. Although FlhC and FlhD have been implicated as virulence determinants, the mechanisms by which these proteins regulate bacterial cytotoxicity to different cell types remains unclear.Aim. This study aimed to evaluate the mechanisms of FlhDC-mediated cytotoxicity to human epithelial cells by S. marcescens.Methodology. Wild-type and mutant bacteria and bacterial secretomes were used to challenge airway and ocular surface cell lines as evaluated by resazurin and calcein AM staining. Pathogenesis was further tested using a Galleria mellonella infection model.Results. The increased cytotoxicity of scrp-31 bacteria and secretomes to both cell lines was eliminated by mutation of flhD and shlA. Mutation of the flagellin gene had no impact on cytotoxicity under any tested condition. Elimination of the phospholipase gene, phlA, had no effect on bacteria-induced cytotoxicity to either cell line, but reduced cytotoxicity caused by secretomes to airway epithelial cells. Mutation of flhD and shlA, but not phlA, reduced bacterial killing of G. https://www.selleckchem.com/products/ri-1.html mellonella larvae.Conclusion. This study indicates that the S. marcescens FlhDC-regulated secreted proteins PhlA and ShlA, but not flagellin, are cytotoxic to airway and ocular surface cells and demonstrates differences in human epithelial cell susceptibility to PhlA.A Gram-stain-negative bacterium, designated I-24T, was isolated from soil of a natural salt meadow. Strain I-24T was aerobic, non-motile, rod-shaped, catalase-positive, oxidase-positive and grew optimally at pH 7 and 25?°C. Comparative 16S rRNA gene analysis indicated that strain I-24T has closest similarities to Spirosoma agri KCTC 52727T (95.9?%) and Spirosoma terrae KCTC 52035T (95.5?%). Strain I-24T contained summed feature 3 (C16??1?ω7c/C16??1?ω6c) and C16??1?ω5c as the major fatty acids, the predominant respiratory quinone was menaquinone MK-7, and the major polar lipids were phosphatidylethanolamine as well as an unidentified phosphoaminolipid. The draft genome of strain I-24T consists of 10?326?072 base pairs with 9153 predicted coding sequences and a G+C content of 47.7?mol%. Clear distinctions between strain I-24T and S. agri KCTC 52727T or S. terrae KCTC 52035T were shown in the pairwise average nucleotide identity results with values of 76.71 and 74.01?%, respectively. Moreover, the digital DNA-DNA relatedness values to these strains were 20.